Saatchis' sister Pubicis Groupe agency Fallon previously handled the European portion of the Expedia business, having won the business in July 2016.
However, Fallon was realigned away from Saatchis and put alongside Leo Burnett in October last year.
The business will now be jointly managed by the Saatchi & Saatchi global headquarters in London and its Team One office in Los Angeles.
The business comprises all brand advertising campaigns comprising TV, digital video and display, social media, and outdoor. Expedia previously worked with a roster of five agencies across worldwide markets.
Magnus Djaba, global president of Saatchis and chief executive of Saatchis London, said: "Expedia’s agenda of working to combine science, creativity and technology to deliver results that haven’t been seen before, mirrors everything we’re trying to do as a network. We couldn’t be more excited."